U.S. Pat. Nos. 4,604,207 and 4,512,898 to Oi et al disclose packing materials for chromatographic use and a method for analysis of an enantiomer using such packing material. The packing material taught by U.S. Pat. No. 4,512,898 comprises an inorganic carrier having hydroxyl groups at the surface thereof having grafted thereon an organosilane derivative. The organosilane derivative can be a urea derivative obtained by reacting an optically active isocyanate with an aminoalkylsilane, an N-carbamoyl amino acid derivative obtained by reacting an optically active amino acid carbamoylated by isocyanate with an aminoalkylsilane and an O-carbamoyl hydroxy acid derivative obtained by reacting an optically active hydroxy acid carbamoylated by isocyanate with an aminoalkylsilane. This packing material is used as a stationary phase for liquid chromatography for separating and analyzing an enantiomer mixture of certain compounds. The packing material disclosed in U.S. Pat. No. 4,604,207 comprises an inorganic carrier having hydroxyl groups at the surface thereof having grafted thereon an .alpha.-arylalkylamine derivative. The .alpha.-arylalkylamine derivative is formed by bonding an optically active .alpha.-arylalkylamine with an aminoalkylsilane through a dibasic carboxylic acid. This packing material is also utilized as a stationary phase for liquid chromatographic analysis of an enantiomer mixture.
U.S. Pat. No. 4,322,310 is directed to chiral supports for the separation and resolution of racemates by chromatography. These chiral supports comprise a chiral organic amine covalently linked via a carbamate, mercaptocarbamate, or urea linkage to a chain of atoms whose other terminus is covalently bonded to a core support.
There are a variety of strategies for the construction of chiral stationary phases used in chromatographic applications. One of the most useful of these strategies involves the synthesis of stationary phases in which a relatively small chiral molecule is chemically bound to an inert support, and in which the chiral molecule so bound contains multiple-interaction sites. Specifically, these sites include (1) aromatic donor-acceptor, (2) hydrogen-bonding (or dipolar), and (3) bulky steric sites, all in proximity to the chiral center.
One theory pertinent to chromatographic separation and resolution of chiral molecules on such stationary phases was described by Pirkle. This theory postulates discrete and specific interactions between functional groups on the resolved chiral molecules (solutes) with discrete, specific and complementary groups on the chiral stationary phase (CSP). For example, if an aromatic pi-acidic group on the solute interacts with a pi-basic group on the CSP, a hydrogen-bond donating group in the solute with a corresponding accepting group in the CSP, and a steric group in the solute with a similar group in the CSP, and if all of these interactions occur essentially simultaneously, then this theory postulates that this interaction results in a high likelihood of effective chiral discrimination, with consequent resolution of the enantiomeric solutes on the chromatographic stationary phase.
An important extension of this theory involves the inherent reciprocality between the chiral solutes and the chiral molecule bound to the stationary phase. The structural features of chiral solutes which make them good candidates for efficient chromatographic resolution are the same structural features which make them conceptually logical candidates as molecules which could be bound to inert supports, so as to serve thereby as new chiral stationary phases. This principle of reciprocality has seldom been explicitly and deliberately utilized for the design of new CSP's. The present invention represents a particularly straightforward, novel and successful application of this concept.